People of all ages, genders and races suffer at some point from various types of pain. This ranges from general muscle aches and headaches, to significant pain from arthritis, acute injuries, surgery related pain as well as pain from chronic conditions. Chronic pain is the leading cause of adult disability in the United States and is one of the most common reasons for patient visits to primary care clinicians. (Leigh J P, Markowitz S B, Fahs M, Shin C, Landrigan P J. Occupational injury and illness in the United States: estimates of costs, morbidity, and mortality. Arch Intern Med 1997; 157:1557-68.)
Conventional treatment with prescribed and over the counter (OTC) drugs such as acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen (e.g., Motrin and Advil) and naproxen (e.g., Aleve and Naprosyn)), COX-2 inhibitor's (e.g., Celebrex), and narcotics have remained the mainstay of current treatments. However, these treatments are typically associated with significant adverse side effects (e.g., gastrointestinal, cardiovascular, and addiction).
NSAIDs are among the most frequently used class of drugs worldwide, with yearly over-the-counter sales amounting to $30 billion. Gastrointestinal safety continues to be a high priority for patients and clinicians when choosing an NSAID treatment for pain. In fact, the gastrointestinal harm induced by NSAIDs may be the most prevalent adverse event associated with any drug class. Clinical manifestations of adverse gastrointestinal events include gastric and duodenal mucosal erosions, ulcers and ulcer complications, dyspepsia, abdominal pain and nausea. Dyspeptic symptoms include epigastric pain, bloating, nausea and heartburn, which account for the most common reason for discontinuation of NSAID therapy. Gastric or duodenal ulceration occurs in about 20% of NSAID users, and 40% of these individuals develop a serious complication. Other problems in the lower gut linked to the use of NSAIDs are gut inflammation, increase in gut permeability, stricture, protein malabsorption, bleeding, and perforation. Therefore, as a result of the widespread use of these agents, the potential for a significant number of adverse events, particularly gastrointestinal related, is high. Gastrointestinal adverse events associated with NSAID use are reported to account for more than 100,000 hospitalizations and more than 15,000 deaths annually. Noteworthy are the numbers of hospitalizations for patients taking long-term, low-dose aspirin who are admitted with upper gastrointestinal bleeding. This accounts for about 10-15% of the hospital admissions for upper gastrointestinal bleeding. The resulting economic costs incurred in managing NSAID related gastrointestinal adverse events are significant; where it is estimated that $0.66-1.25 of every dollar spent on the cost of the NSAID is associated with treating adverse events.
Selective (COX-2) inhibitors have demonstrated improved gastrointestinal tract safety over traditional NSAIDs drugs. There is important evidence from clinical trials showing that compared with traditional NSAIDs, COX-2 inhibitors are associated with a reduced rate of serious GI events such as bleeding, perforation and obstruction, and other symptoms such as dyspepsia, as well as a reduced requirement for concomitant gastroprotective therapies such as proton pump inhibitors. This relative benefit may be related to a lack of COX-1-mediated inhibition of gastric mucous production and a lack of effect on platelet thromboxane production. However, the differential effects of COX-2 inhibitors compared with traditional NSAIDs on platelet aggregation, prostacyclin/thromboxane balance, and inflammatory mediators involved in the development of atherosclerosis have also led to concerns that there is a physiological basis for COX-2 inhibitors to increase the risk for thrombotic events. These negative cardiotoxic effects (myocardial infarctions) of the COX-2 inhibitors were first documented in the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial and the Celecoxib Long-term Arthritis Safety Study (CLASS). Although the cardiotoxic effects were thought to be limited to myocardial infarctions, a subsequent meta analysis showed an increase in the occurrence of arrhythmias in COX-2 treated patients as well. The ensuing body of evidence relating to adverse cardiovascular outcomes prompted the FDA to remove rofecoxib (Vioxx®) from the market and led to modified warnings and use of Celecoxib (Celebrex®). Additionally, resulting changes to pain treatment recommendations have led to a significant decline in the use of the COX-2 inhibitors.
Because of the widespread use of NSAIDs and COX-2 inhibitors, the risks associated with their use are of increasing concern. In the recently concluded 2009 American Geriatrics Society (AGS) annual meeting; as a result of their troubling side effect profiles, the revised AGS guidelines on the management of persistent pain to be published in the August issue of the Journal of the American Geriatrics Society adopted the position and will advise physicians to have their elderly patients avoid the use of NSAIDs and COX-2 inhibitors and consider the use of low-dose opioid therapy instead. This position reflects general safety concerns with the use of these agents.
As the population ages, more patients will experience osteoarthritis, rheumatoid arthritis, chronic back pain, chronic musculoskeletal injuries, and migraines. Other ailments such as pain from overexertion, perimensual pain, etc, will also necessitate treatment. It is therefore very likely that gastrointestinal problems will continue to increase as the use of the traditional nonselective NSAIDs in the United States increases because of the concern for cardiovascular complications associated with the COX-2 inhibitors. The elderly are especially at risk for gastrointestinal events, including serious complications.
There therefore remains a need for just as effective, but safer alternatives for the treatment of pain.
Many anecdotal as well as recent studies support the use of natural remedies (herbal) for relief of pain. Historically herbal remedies have not only been reported as effective, but they have been used to treat various ailments and conditions and generally have had very low risk profiles. But such remedies are not typically as effective as pharmaceutical pain relief products that are currently available OTC or by prescription.